Research is being conducted to determine the absorption, tissue distribution, metabolism and excretion of two polychlorinated biphenyl isomers, 2,5,2',5'-tetrachlorobiphenyl (TCB) and 2,4,5,2'4'5'-hexachlorobiphenyl (HCB) in the nonhuman primate and rat. In addition, experiments are underway to determine the interaction of metabolites of these two PCB isomers with cellular macromolecules under in vivo and in vitro conditions. A considerable difference in the rate of excretion of the PCB isomers was encountered in both animal species, with the majority of the TCB isomer being readily metabolized and excreted while the more highly chlorinated HCB compound was metabolized and excreted rather slowly. The major source of excretion with both isomers was via the biliary route. In addition to the monohydroxylated metabolites, transdihydrodiols have been identified in excreta of rats and monkeys. The latter metabolite suggests that the TCB is metabolized through an arene oxide intermediate. Metabolites isolated from the bile were excreted primarily as conjugated metabolites. It has also been shown that TCB incubated with monkey liver microsomes in a proper generating system covalently bind to RNA and protein. The chemical nature of this binding is presently under investigation. It has also been shown that TCB is toxic to cultured cell suspensions in concentrations greater than 15 micron g per ml of media. In addition, cell transformation has been recorded in C3H/10T1/2 cells exposed to TCB. Transformed cells have been injected into susceptible hosts in order to determine the tumor producing ability. Progress is being made in the synthesis of the arene oxide intermediate metabolite of TCB. Once available this metabolite will be used for the in vitro binding studies to evaluate its ability to produce cell transformation and tumors. BIBLIOGRAPHIC REFERENCES: Allen, J. R., Carstens, L.A. and Abrahamson, L.J. Responses of rats exposed to polychlorinated biphenyls for fifty-two weeks. I. Comparison of tissue levels of PCB and biological changes. Archives of Environmental Contamination and Toxicology 4, 409-419 (1976). Van Miller, J.P., Marlar, R.J. and Allen, J.R. Tissue distribution and excretion of 3H tetrachlorodibenzo-p-dioxin in nonhuman primates and rats. Food and Cosmetics Toxicology 14, 31-34 (1976).